DESCRIPTION (Applicant's abstract): Exercise causes a transient increase in the NMR transverse relaxation time (T2) of water in active skeletal muscles. The increase is easily observed as increased signal intensity in T2-weighted MR images, and has already been used in many studies to identify which muscles were recruited during various motor tasks. The ultimate goal of this proposal is to further exploit the activity-induced increase in muscle T2 as a quantitative measure of muscle recruitment. This would permit non-invasive examination of disease severity, and monitoring of the efficacy of rehabilitation therapy, in patients with neuromuscular disease. There are two prerequisites to achieve this goal: first, the physiologic factors that cause T2 to increase must be clearly understood, and second, the range of conditions under which the T2 increase is directly related to motor activity must be defined. The first Aim of this proposal will determine the physiologic factors which cause muscle T2 to increase during contraction. In contrast to the prevailing view, preliminary studies indicate that a long T2 component corresponding to extracellular fluid is not resolved in intact muscles of animals or humans, and that the T2 increase during activity is not due to increased extracellular fluid. Further experiments in intact and isolated, perfused cat muscles will directly test this hypothesis. Additional studies in both rat and cat muscles will test the hypotheses that the T2 increase is caused by changes in intracellular fluid, osmolarity, and pH. The second aim will fully define the relationships between T2 vs. absolute exercise intensity, relative exercise intensity, and exercise duration in human subjects. In addition, the reproducibility of the T2 response after manipulations such as prior exercise, muscle damage, and edema will be examined. These experiments will provide the foundation for development of quantitative protocols for measuring muscle recruitment in clinical patients by MRI.